tbuckley/cabot-search huggingface dataset:
Author Correction: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021
Authors: Laura C. Coates, Enrique R. Soriano, Nadia Corp, Heidi Bertheussen, Kristina Callis Duffin, Cristiano B. Campanholo, Jeffrey Chau, Lihi Eder, Daniel G. Fernández-Ávila, Oliver FitzGerald, Amit Garg, Dafna D. Gladman, Niti Goel, Philip S. Helliwell, M. Elaine Husni, Deepak R. Jadon, Arnon Katz, Dhruvkumar Laheru, John Latella, Ying-Ying Leung, Christine Lindsay, Ennio Lubrano, Luis Daniel Mazzuoccolo, Philip J. Mease, Denis O’Sullivan, Alexis Ogdie, Wendy Olsder, Penelope Esther Palominos, Lori Schick, Ingrid Steinkoenig, Maarten de Wit, D. A. van der Windt, Arthur Kavanaugh, Cristiano Campanholo, Oliver Fitzgerald, Dafna Gladman, Philip Helliwell, M. Elaine Husni, Dhrukumar Laheru, Ying-Ying Leung, Ennio Lubrano, Luis Daniel Mazzuoccolo, Philip J. Mease, Alexis Ogdie, Penelope Esther Palominos
Journal: Nature Reviews Rheumatology (2022)
Breast Cancer Metastatic Dormancy and Relapse: An Enigma of Microenvironment(s)
Authors: Islam E. Elkholi, Andréane Lalonde, Morag Park, Jean-François Côté
Journal: Cancer Research (2022)

Abstract Multiple factors act in concert to define the fate of disseminated tumor cells (DTC) to enter dormancy or develop overt metastases. Here, we review these factors in the context of three stages of the metastatic cascade that impact DTCs. First, cells can be programmed within the primary tumor microenvironment to promote or inhibit dissemination, and the primary tumor can condition a premetastatic niche. Then, cancer cells from the primary tumor spread through hematogenous and lymphatic routes, and the primary tumor sends cues systematically to regulate the fate of DTCs. Finally, DTCs home to their metastatic site, where they are influenced by various organ-specific aspects of the new microenvironment. We discuss these factors in the context of breast cancer, where about one-third of patients develop metastatic relapse. Finally, we discuss how the standard-of-care options for breast cancer might affect the fate of DTCs.
Cell Competition in Carcinogenesis
Authors: Esha Madan, António M. Palma, Vignesh Vudatha, Jose G. Trevino, Kedar Nath Natarajan, Robert A. Winn, Kyoung Jae Won, Trevor A. Graham, Ronny Drapkin, Stuart A.C. McDonald, Paul B. Fisher, Rajan Gogna
Journal: Cancer Research (2022)

Abstract The majority of human cancers evolve over time through the stepwise accumulation of somatic mutations followed by clonal selection akin to Darwinian evolution. However, the in-depth mechanisms that govern clonal dynamics and selection remain elusive, particularly during the earliest stages of tissue transformation. Cell competition (CC), often referred to as 'survival of the fittest' at the cellular level, results in the elimination of less fit cells by their more fit neighbors supporting optimal organism health and function. Alternatively, CC may allow an uncontrolled expansion of super-fit cancer cells to outcompete their less fit neighbors thereby fueling tumorigenesis. Recent research discussed herein highlights the various non–cell-autonomous principles, including interclonal competition and cancer microenvironment competition supporting the ability of a tumor to progress from the initial stages to tissue colonization. In addition, we extend current insights from CC-mediated clonal interactions and selection in normal tissues to better comprehend those factors that contribute to cancer development.
Monounsaturated and Diunsaturated Fatty Acids Sensitize Cervical Cancer to Radiation Therapy
Authors: Naoshad Muhammad, Fiona Ruiz, Jennifer Stanley, Ramachandran Rashmi, Kevin Cho, Kay Jayachandran, Michael C. Zahner, Yi Huang, Jin Zhang, Stephanie Markovina, Gary J. Patti, Julie K. Schwarz
Journal: Cancer Research (2022)

Abstract Obesity induces numerous physiological changes that can impact cancer risk and patient response to therapy. Obese patients with cervical cancer have been reported to have superior outcomes following chemoradiotherapy, suggesting that free fatty acids (FFA) might enhance response to radiotherapy. Here, using preclinical models, we show that monounsaturated and diunsaturated FFAs (uFFA) radiosensitize cervical cancer through a novel p53-dependent mechanism. UFFAs signaled through PPARγ and p53 to promote lipid uptake, storage, and metabolism after radiotherapy. Stable isotope labeling confirmed that cervical cancer cells increase both catabolic and anabolic oleate metabolism in response to radiotherapy, with associated increases in dependence on mitochondrial fatty acid oxidation for survival. In vivo, supplementation with exogenous oleate suppressed tumor growth in xenografts after radiotherapy, an effect that could be partially mimicked in tumors from high fat diet–induced obese mice. These results suggest that supplementation with uFFAs may improve tumor responses to radiotherapy, particularly in p53 wild-type tumors. Significance: Metabolism of monounsaturated and diunsaturated fatty acids improves the efficacy of radiotherapy in cancer through modulation of p53 activity. See related commentary by Jungles and Green, p. 4513
Misrepresentation and Nonadherence Regarding COVID-19 Public Health Measures
Authors: Andrea Gurmankin Levy, Alistair Thorpe, Laura D. Scherer, Aaron M. Scherer, Frank A. Drews, Jorie M. Butler, Nicole Burpo, Holly Shoemaker, Vanessa Stevens, Angela Fagerlin
Journal: JAMA Network Open (2022)

The effectiveness of public health measures implemented to mitigate the spread and impact of SARS-CoV-2 relies heavily on honesty and adherence from the general public.To examine the frequency of, reasons for, and factors associated with misrepresentation and nonadherence regarding COVID-19 public health measures.This survey study recruited a national, nonprobability sample of US adults to participate in an online survey using Qualtrics online panels (participation rate, 1811 of 2260 [80.1%]) from December 8 to 23, 2021. The survey contained screening questions to allow for a targeted sample of one-third who had had COVID-19, one-third who had not had COVID-19 and were vaccinated, and one-third who had not had COVID-19 and were unvaccinated.The survey assessed 9 different types of misrepresentation and nonadherence related to COVID-19 public health measures and the reasons underlying such behaviors. Additional questions measured COVID-19-related beliefs and behaviors and demographic characteristics.The final sample included 1733 participants. The mean (SD) participant age was 41 (15) years and the sample predominantly identified as female (1143 of 1732 [66.0%]) and non-Hispanic White (1151 of 1733 [66.4%]). Seven hundred twenty-one participants (41.6%) reported misrepresentation and/or nonadherence in at least 1 of the 9 items; telling someone they were with or about to be with in person that they were taking more COVID-19 preventive measures than they actually were (420 of 1726 [24.3%]) and breaking quarantine rules (190 of 845 [22.5%]) were the most common manifestations. The most commonly endorsed reasons included wanting life to feel normal and wanting to exercise personal freedom. All age groups younger than 60 years (eg, odds ratio for those aged 18-29 years, 4.87 [95% CI, 3.27-7.34]) and those who had greater distrust in science (odds ratio, 1.14 [95% CI, 1.05-1.23]) had significantly higher odds of misrepresentation and/or nonadherence for at least 1 of the 9 items.In this survey study of US adults, nearly half of participants reported misrepresentation and/or nonadherence regarding public health measures against COVID-19. Future work is needed to examine strategies for communicating the consequences of misrepresentation and nonadherence and to address contributing factors.
Tracheal Y-Stent–induced Carinal Reunion after Complicated Aerodigestive Fistula
Authors: Russell J. Miller, Nicholas J. Rohrhoff, Matthew M. Nobari, George Z. Cheng
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Tracheal Y-Stent–induced Carinal Reunion after Complicated Aerodigestive Fistula." American Journal of Respiratory and Critical Care Medicine, 207(5), pp. 613–614
Trends in Obesity Prevalence Among Patients Enrolled in Clinical Trials for Obesity-Related Cancers, 1986 to 2016
Authors: Riha Vaidya, Cathee Till, Heather Greenlee, Dawn L. Hershman, Joseph M. Unger
Journal: JAMA Network Open (2022)

Importance Obesity rates have risen in the United States since the 1980s. Several studies have shown links between obesity and the incidence of specific cancer types, but none have systematically examined obesity prevalence at the time of cancer diagnosis, or among clinical trial participants, all of which may affect clinical outcomes. Objective To examine the prevalence of obesity and, separately, overweight and obesity over 30 years among patients with cancer enrolled in clinical treatment trials for obesity-related cancers; and to compare trends with corresponding trends in the US. Design, Setting, and Participants This cohort study examined clinical treatment trials for obesity-related cancers conducted by the SWOG Cancer Research Network at community and academic sites. Participants included adult patients enrolled in phase 2 or phase 3 clinical treatment trials in obesity-related cancers between 1986 and 2016. Statistical analysis was performed from June 2020 to July 2022. Exposures Year of enrollment to a clinical trial. Main Outcomes and Measures Prevalence of obesity (body mass index [BMI] ≥ 30) and overweight or obesity (BMI &amp;amp;gt; 25) at the time of clinical trial enrollment. Multivariable logistic regression analysis, adjusted for demographic and clinical factors, was used to analyze patient height and weight collected at clinical trial enrollment. Results Among 23 926 patients (median [IQR] age, 58 [51-66] years; 17 594 [73.5%] female; 969 [4.0%] Hispanic, 2173 [9.1%] non-Hispanic Black, 19 890 [83.1%] non-Hispanic White) enrolled between 1986 and 2016, unadjusted obesity rates increased from 23.5% (in 1986 to 1990 [n = 657]) to 42.3% (in 2011 to 2016 [n = 836]). There was an increasing linear trend in obesity (odds ratio [OR], 1.23 for each 5-year increase; 95% CI, 1.21-1.26; P &amp;amp;lt; .001), which persisted after covariate adjustment for demographic and clinical characteristics. Findings were consistent for the combined prevalence of overweight and obesity. The observed overall increasing trend in obesity prevalence from 1999-2000 to 2015-2016 was greater in trial patients (21.3% [SE = 0.7] to 49.1% [SE = 1.6]) than in US adults (30.5% [SE = 1.5] to 39.6% [SE = 1.6]) ( P for trend = .03), but was similar to US cancer survivors (18.9% [SE = 1.9] to 42.2% [SE = 2.1]; P for trend = .31). Conclusions and Relevance This cohort study found that patients with cancer and obesity are currently well-represented in cancer clinical trials, increasing confidence that trial findings are generalizable to patients with obesity in clinical practice. Availability of data on height and weight at diagnosis through cancer registries will enable a more rigorous analysis of obesity prevalence among patients with cancer.
Time-restricted eating with or without low-carbohydrate diet reduces visceral fat and improves metabolic syndrome: A randomized trial
Authors: Mingqian He, Jingya Wang, Qian Liang, Meng Li, Hui Guo, Yue Wang, Cuomu Deji, Jing Sui, Ya-wen Wang, Yufeng Liu, Yixuan Zheng, Buyue Qian, Huaixi Chen, Mao Ma, Shi Su, Hui Geng, Wen-xu Zhou, Xiaoxiao Guo, Wen-zhi Zhu, Meng Zhang, Ziyi Chen, Patrick C.N. Rensen, Chi-chung Hui, Yanan Wang, Bingyin Shi
Journal: Cell Reports Medicine (2022)

Overconsumption of carbohydrate-rich food combined with adverse eating patterns contributes to the increasing incidence of metabolic syndrome (MetS) in China. Therefore, we conducted a randomized trial to determine the effects of a low-carbohydrate diet (LCD), an 8-h time-restricted eating (TRE) schedule, and their combination on body weight and abdominal fat area (i.e., primary outcomes) and cardiometabolic outcomes in participants with MetS. Compared with baseline, all 3-month treatments significantly reduce body weight and subcutaneous fat area, but only TRE and combination treatment reduce visceral fat area (VFA), fasting blood glucose, uric acid (UA), and dyslipidemia. Furthermore, compared with changes of LCD, TRE and combination treatment further decrease body weight and VFA, while only combination treatment yields more benefits on glycemic control, UA, and dyslipidemia. In conclusion, without change of physical activity, an 8-h TRE with or without LCD can serve as an effective treatment for MetS (ClinicalTrials.gov: NCT04475822).
Artificial intelligence for multimodal data integration in oncology
Authors: Jana Lipkova, Richard J. Chen, Bowen Chen, Ming Y. Lu, Matteo Barbieri, Daniel Shao, Anurag J. Vaidya, Chengkuan Chen, Luoting Zhuang, Drew F.K. Williamson, Muhammad Shaban, Tiffany Y. Chen, Faisal Mahmood
Journal: Cancer Cell (2022)

In oncology, the patient state is characterized by a whole spectrum of modalities, ranging from radiology, histology, and genomics to electronic health records. Current artificial intelligence (AI) models operate mainly in the realm of a single modality, neglecting the broader clinical context, which inevitably diminishes their potential. Integration of different data modalities provides opportunities to increase robustness and accuracy of diagnostic and prognostic models, bringing AI closer to clinical practice. AI models are also capable of discovering novel patterns within and across modalities suitable for explaining differences in patient outcomes or treatment resistance. The insights gleaned from such models can guide exploration studies and contribute to the discovery of novel biomarkers and therapeutic targets. To support these advances, here we present a synopsis of AI methods and strategies for multimodal data fusion and association discovery. We outline approaches for AI interpretability and directions for AI-driven exploration through multimodal data interconnections. We examine challenges in clinical adoption and discuss emerging solutions.
Placebo Response to Oral Administration in Osteoarthritis Clinical Trials and Its Associated Factors
Authors: Xin Wen, Jieren Luo, Yiying Mai, Yang Li, Ying Cao, Zewei Li, Shun Han, Quanyi Fu, Qingshan Zheng, Changhai Ding, Zhaohua Zhu, Lujin Li
Journal: JAMA Network Open (2022)

Importance In osteoarthritis (OA) clinical trials, a placebo is often used as control. Therefore, a thorough understanding of the placebo response is important for guiding drug development in OA. Objective To develop an oral placebo response model for OA. Data Sources PubMed, EMBASE, and Cochrane Library databases were searched systematically from January 1, 1991, to July 2, 2022. Study Selection Randomized double-blind placebo-controlled trials of patients with primary OA were included. The interventions and placebo were administered orally. A total of 3032 trials were identified; of these, 130 (4.3%) met the inclusion criteria. Data Extraction and Synthesis Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, dosage form of the placebo, sample size, proportion of patients who previously used nonsteroidal anti-inflammatory drugs, publication year, intervention categories, Kellgren-Lawrence grades, proportion of White patients, duration of pain, funding source, and risk of bias were extracted. A model-based meta-analysis was used to evaluate the time course of the placebo response in OA treatment and estimate the influencing factors. For subgroup analyses, a meta-analysis with a random-effects model was used to summarize the typical values of the model parameters and their SEs. Main Outcomes and Measures The primary end point was the time course of the oral placebo response on the WOMAC pain, stiffness, and function subscale scores. Results The 130 trials selected for analysis included 12 673 participants (mean age, 59.9 years; 68.9% women). The baseline scores of WOMAC pain, stiffness, and function subscales were found to be significantly associated with the placebo response. The placebo response reached 90% of its maximum response between 5 and 7 weeks. The placebo responses on the WOMAC subscales were also associated with the sample size, proportion of patients who had previously used nonsteroidal anti-inflammatory drugs, intervention drugs, and publication year. Conclusions and Relevance In this study, an oral placebo response model of OA was developed that may quantitatively describe the placebo response at different baseline levels of symptoms. The findings may provide valuable references for future clinical trial design and decision-making.
Mendelian Randomization Analysis Reveals a Complex Genetic Interplay among Atopic Dermatitis, Asthma, and Gastroesophageal Reflux Disease
Authors: Kwangmi Ahn, Raymond B. Penn, Satish Rattan, Reynold A. Panettieri, Benjamin F. Voight, Steven S. An
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Gastroesophageal reflux disease (GERD) is commonly associated with atopic disorders, but cause–effect relationships remain unclear. Objectives: We applied Mendelian randomization analysis to explore whether GERD is causally related to atopic disorders of the lung (asthma) and/or skin (atopic dermatitis [AD]). Methods: We conducted two-sample bidirectional Mendelian randomization to infer the magnitude and direction of causality between asthma and GERD, using summary statistics from the largest genome-wide association studies conducted on asthma (Ncases = 56,167) and GERD (Ncases = 71,522). In addition, we generated instrumental variables for AD from the latest population-level genome-wide association study meta-analysis (Ncases = 22,474) and assessed their fidelity and confidence of predicting the likely causal pathway(s) leading to asthma and/or GERD. Measurements and Main Results: Applying three different methods, each method revealed similar magnitude of causal estimates that were directionally consistent across the sensitivity analyses. Using an inverse variance–weighted method, the largest effect size was detected for asthma predisposition to AD (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.34–1.59), followed by AD to asthma (OR, 1.34; 95% CI, 1.24–1.45). A significant association was detected for genetically determined asthma on risk of GERD (OR, 1.06; 95% CI, 1.03–1.09) but not genetically determined AD on GERD. In contrast, GERD equally increased risks of asthma (OR, 1.21; 95% CI, 1.09–1.35) and AD (OR, 1.21; 95% CI, 1.07–1.37). Conclusions: This study uncovers previously unrecognized causal pathways that have clinical implications in European-ancestry populations: 1) asthma is a causal risk for AD, and 2) the predisposition to AD, including asthma, can arise from specific pathogenic mechanisms manifested by GERD.
Peroxynitrite in the tumor microenvironment changes the profile of antigens allowing escape from cancer immunotherapy
Authors: Evgenii N. Tcyganov, Emilio Sanseviero, Douglas Marvel, Thomas Beer, Hsin-Yao Tang, Peter Hembach, David W. Speicher, Qianfei Zhang, Laxminarasimha R. Donthireddy, Ali Mostafa, Sabina Tsyganova, Vladimir Pisarev, Terri Laufer, Dmitriy Ignatov, Soldano Ferrone, Christiane Meyer, Hélène Maby-El Hajjami, Daniel E. Speiser, Sooner Altiok, Scott Antonia, Xiaowei Xu, Wei Xu, Cathy Zheng, Lynn M. Schuchter, Ravi K. Amaravadi, Tara C. Mitchell, Giorgos C. Karakousis, Zhe Yuan, Luis J. Montaner, Esteban Celis, Dmitry I. Gabrilovich
Journal: Cancer Cell (2022)
In situ cell-type-specific cell-surface proteomic profiling in mice
Authors: S. Andrew Shuster, Jiefu Li, URee Chon, Miley C. Sinantha-Hu, David J. Luginbuhl, Namrata D. Udeshi, Dominique Kiki Carey, Yukari H. Takeo, Qijing Xie, Chuanyun Xu, D.R. Mani, Shuo Han, Alice Y. Ting, Steven A. Carr, Liqun Luo
Journal: Neuron (2022)

Cell-surface proteins (CSPs) mediate intercellular communication throughout the lives of multicellular organisms. However, there are no generalizable methods for quantitative CSP profiling in specific cell types in vertebrate tissues. Here, we present in situ cell-surface proteome extraction by extracellular labeling (iPEEL), a proximity labeling method in mice that enables spatiotemporally precise labeling of cell-surface proteomes in a cell-type-specific environment in native tissues for discovery proteomics. Applying iPEEL to developing and mature cerebellar Purkinje cells revealed differential enrichment in CSPs with post-translational protein processing and synaptic functions in the developing and mature cell-surface proteomes, respectively. A proteome-instructed in vivo loss-of-function screen identified a critical, multifaceted role for Armh4 in Purkinje cell dendrite morphogenesis. Armh4 overexpression also disrupts dendrite morphogenesis; this effect requires its conserved cytoplasmic domain and is augmented by disrupting its endocytosis. Our results highlight the utility of CSP profiling in native mammalian tissues for identifying regulators of cell-surface signaling.
Broadening Our SCOPE of Understanding Patent Foramen Ovale High-risk Features and Stroke—Progress and Nuance
Authors: Arielle P. Davis, David L. Tirschwell
Journal: JAMA Neurology (2022)

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Cancer Clinical Trial Enrollment in Older vs Younger Adults
Authors: Li-Wen Huang, Sunny Wang
Journal: JAMA Network Open (2022)

Mina S. Sedrak, MD, MS; Jingran Ji, MD; Abhay Tiwari, BS; Supriya G. Mohile, MD, MS; William Dale, MD, PhD; Jennifer G. Le-Rademacher, PhD
Microsomal triglyceride transfer protein regulates intracellular lipolysis in adipocytes independent of its lipid transfer activity
Authors: Sujith Rajan, Peter Hofer, Amanda Christiano, Matthew Stevenson, Louis Ragolia, Eugenia Villa-Cuesta, Susan K. Fried, Raymond Lau, Collin Braithwaite, Rudolf Zechner, Gary J. Schwartz, M. Mahmood Hussain
Journal: Metabolism (2022)